Rectal gastrointestinal stromal tumors are rare. To date, 12 gastrointestinal stromal tumors have been reported as pelvic vaginal masses. We describe a rectovaginal tumor in a 39-year-old woman. The tumor frequently recurred after multiple surgical excisions and interrupted imatinib treatment without metastasizing. Magnetic resonance tomography demonstrated a partial response under imatinib. The patient was alive with stable disease under imatinib 44 months from initial diagnosis. Molecular analysis showed a somatic 6–base pair deletion in exon 11 of c-KIT (W557_K558del) in both the primary tumor and the third recurrence; the recurrence had an additional exon 17 mutation (N822K). Comparative genomic hybridization analysis of the primary tumor showed loss of 14q and gain of 1q. Recurrence showed complete loss of nuclear p16 expression. Molecular studies and p16 status confirmed the typical characteristics of gastrointestinal stromal tumors with an aggressive phenotype underscoring the need for a special interdisciplinary treatment and for achieving complete local excision with free margins.

Albumin was found to be a structural constituent of chicken myofibrils. Its subcellular localization as shown by electron microscopy demonstrated highest concentrations of albumin in the region where the thin and thick filaments overlap. In addition, evidence is presented in favour of albumin synthesis in muscle. These results suggest a physiological role of an albumin in muscle, most probably in the fatty acid metabolism.

Die Initiative »Wissenstransfer Oberflächentechnik« soll bestehende und erwartete Potenziale moderner Oberflächentechnik für die deutsche Wirtschaft besser zugänglich machen. Ziele sind Innovationsbeschleunigung, Wissenstransfer und Effektivitätsgewinne in Richtung Wettbewerbsfähigkeit und technologischer Leistungsfähigkeit. Zielgruppe sind insbesondere kleine und mittlere, innovationsorientierte Unternehmen. Die Initiative wird vom VDI-Technologiezentrum Düsseldorf im Auftrag des Bundesministeriums für Bildung und Forschung durchgeführt. Einige Ergebnisse liegen bereits vor. Knowledge Transfer in Surface Technology »Wissenstransfer Oberflächentechnik« (knowledge transfer in surface technology) aims at existing and expected potentials of modern surface technology for the german economy. The main goals are knowledge transfer, acceleration of innovation and growth of competitiveness and technological performance capability. The target group mainly consists of Small and Medium Enterprises orientated to innovation. This initiative is untertaken by the VDI-Technology Center Düsseldorf on behalf of the German Ministery of Education and Research. Preliminary results are already available.

We investigated steady-state movement-related cortical potentials elicited by fast repetitive movements (1/sec@rpar; with 50-channel EEG. The experimental design comprised a comparison @lpar;a@rpar; between unilateral movements of the digits and the toes and (b) between metronome-paced and self-paced initiation of the movements. A distinct biphasic pattern of electrical activity following movement onset was observed, namely a frontal negative peak at a latency of 90 ms (post-MP100) and a frontal positive peak at a latency of 310 ms )post-MP300(. Pacing exerted its effects mainly on the amplitude and on the latency of the post-MP300. Source analysis revealed that both peaks could be modelled by a single source. The source locations were highly reproducible across the metronome-paced and self-paced conditions, and, they followed the expected somatotopic organisation.

BACKGROUND:Enteroviruses were detected in up to 50% in myocardium of patients with myocarditis and dilated cardiomyopathy, the latter being considered as a result of a prior subclinical myocarditis. A wide range of other infectious agents are being discussed as pathogens, often only based on reports of single cases. Adenovirus genome was recently identified in a significant number in the myocardium of paediatric patients with myocarditis. However, data on the role of adenoviruses for the aetiopathogenesis of myocarditis in adult patients is missing so far. Therefore, we studied the prevalence of adenoviral and enteroviral genome in myocardium of adults with myocarditis and dilated cardiomyopathy.METHODS:15 patients were diagnosed at baseline with myocarditis, 16 patients with dilated cardiomyopathy according to clinical and histological criteria. Endomyocardial biopsies of these patients and 8 control patients with non-infectious heart diseases were evaluated by polymerase chain reactions for enterovirus and adenovirus genome.RESULTS:Enteroviral genome was detected in 27.3% patients with myocarditis or dilated cardiomyopathy, whereas adenoviral genome was not identified in any patient. Samples from control subjects systematically yielded negative results.CONCLUSIONS:From our data, it seems doubtful that adenoviruses are major pathogens of myocarditis or DCM, whereas enterovirus genome was identified in a significant number of patients with both diseases.

Persistent infections with a cardiotropic enterovirus, e.g. coxsackievirus B2 (CVB2), cause chronic myocarditis and eventually congestive heart failure. Therefore, the antiviral activity of WIN 54954, a capsid binding antiviral agent that inhibits enterovirus uncoating, was studied in persistently CVB2-infected cultures of human myocardial fibroblasts. Cultures displayed a typical carrier state infection with virus titers of 3.9±1.6×105 plaque forming units (PFU)/ml and 0.99% infected cells. WIN 54954 (0.025–1 μg/ml) application was started 7 days after infection of the cultures. Compared to the WIN 54954 concentration resulting in a 90% plaque number reduction (EC90=0.197 μg/ml) in acutely infected Vero cells, WIN 54954 reduced virus yields of myocardial fibroblast cultures more efficiently, e.g. more than 100 fold (99%) with 0.025 μg/ml after 4 days of application. Antiviral effects of WIN 54954 increased with application time and at 0.025 μg/ml Win 54954 completely inhibited infectious virus progeny after 16 days. Increasing the WIN 54954 concentration up to 1 μg/ml did not cause a greater inhibition of virus replication. In situ hybridization demonstrated that at 0.1 μg/ml WIN 54954 reduced the number of infected cells from 0.99 to 0.18%, although a complete eradication of CVB2-infected cells was not achieved at concentrations as high as 1 μg/ml. In conclusion, the results indicate that low concentrations of WIN 54954 are effective in treating persistent enterovirus infections of myocardial fibroblasts, although a complete eradication of the infection is not achieved with WIN 54954 as a single antiviral agent.

As enterovirus infections of the heart cause myocarditis and eventually congestive heart failure, the antiviral activity of ribavirin was studied in coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial fibroblasts. Cultures were infected 7 days before application of ribavirin and effects were evaluated over a period of 16 days by plaque assays and in situ hybridization. Compared to the low antiviral activity in HeLa cells, ribavirin was highly active in reducing infectious virus yields in human myocardial fibroblasts, for example, to 2.0 x 10(3) pfu/ml with 25 microg/ml and to 1.3 x 10(2) pfu/ml with 50 microg/ml (4.3 x 10(4) pfu/ml in infected controls). Moreover, 100 microg ribavirin/ml completely suppressed infectious virus progeny in two of three cultures, and reduced the number of infected cells from 14.3 to 0.3% as determined by in situ hybridization, whereas up to 3200 microg ribavirin/ml did not result in a significant cytotoxic effect. Interaction with interferon-alpha (IFN-alpha) was additive to slightly synergistic in reducing the number of infected cells and virus yields. In conclusion, our results suggest a cell-specific high activity of ribavirin in human myocardial fibroblasts and indicate the importance of using organ-specific cells for testing antiviral agents in myocarditis. Furthermore, the usefulness of in situ hybridization for determining the long term effects of antivirals in carrier state cell cultures was demonstrated.

Detection of enterovirus RNA in endomyocardial biopsies (EMB) by reverse transcription/polymerase chain reaction (RT-PCR) is currently the preferred diagnostic procedure in suspected enterovirus heart disease (EHD), which can present clinically as myocarditis, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). EMB and peripheral blood mononuclear cells (PBMC) of 44 patients with suspected EHD were examined by nested RT-PCR to investigate whether the myocardial enterovirus infection is limited to the heart or is generalized. Enterovirus RNA was detected in EMB, but not in PBMC, of 8 patients (3 of these suffered from ARVC), whereas EMB of 16 controls and PBMC of 45 controls were negative. In addition, enterovirus RNA was demonstrated in PBMC, but not in EMB, of a single patient with suspected EHD. A high sequence homology of the amplicons to coxsackievirus B3 was demonstrated in 7 patients, and to coxsackievirus B2 in two patients. In order to evaluate whether the myocardial enterovirus infection was acute or persistent, neutralization and complement fixation tests were performed for antibodies against the serotypes indicated by the nucleic acid sequences. Neutralizing antibodies were detected in the sera of all 9 patients, but complement fixing antibodies were demonstrated only in one EHD patient and in the patient positive for enterovirus RNA in PBMC. In conclusion, the molecular and serological data demonstrate that CVB3 predominates as cardiotropic enterovirus, and that the enterovirus replication is limited to the heart in EHD. Serological results support the hypothesis of myocardial enterovirus RNA persistence in spite of neutralizing antibodies.

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population, Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml. whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (<50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy. (C) 1995 Academic Press Limited